Enhanced mRNA cap methylation increases cyclin D1 expression and promotes cell transformation

Oncogene. 2010 Feb 11;29(6):930-6. doi: 10.1038/onc.2009.368. Epub 2009 Nov 16.

Abstract

Cap-dependent mRNA translation requires the methylation of the mRNA guanosine cap by RNA guanine-7-methyltransferase (RNMT). mRNA cap methylation was recently described to be rate-limiting for a subset of mRNAs, and to be enhanced by expression of c-Myc and E2F1, although the biological significance of this finding was not investigated. Here, it is reported that increased RNMT expression enhances cellular mRNA cap methyltransferase activity, promotes mammary epithelial cell transformation and cooperates with H-RasV12 or c-Myc to promote fibroblast cell transformation. Cyclin D1 is a prominent oncogene in epithelial tumours. A significant fraction of Cyclin D1 mRNA was found to be unmethylated on the mRNA cap and thus dormant in mammary epithelial cells. Cyclin D1 expression was increased by enhanced mRNA cap methylation. In summary, this report shows that mRNA cap methylation is rate-limiting for expression of an oncogene and cell transformation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Cell Transformation, Neoplastic*
  • Cyclin D1 / biosynthesis*
  • Cyclin D1 / genetics
  • Cyclin D1 / metabolism
  • Humans
  • Kinetics
  • Mammary Glands, Human / cytology
  • Methylation
  • Methyltransferases / metabolism
  • Protein Biosynthesis
  • Proto-Oncogene Proteins c-myc / metabolism
  • RNA Caps / metabolism*
  • Up-Regulation*
  • ras Proteins / metabolism

Substances

  • Proto-Oncogene Proteins c-myc
  • RNA Caps
  • Cyclin D1
  • Methyltransferases
  • mRNA (guanine(N7))-methyltransferase
  • ras Proteins